Using implantable medical devices to augment noninvasive cardiac mapping

ABSTRACT

An example method includes establishing a communications link between an electrophysiology (EP) monitoring system and an implantable medical device (IMD). IMD electrical data is received at the monitoring system via the communications link. The IMD electrical data may be synchronized with EP measurement data to provide synchronized electrical data based on timing of a synchronization signal sensed by an IMD electrode and/or EP electrodes. The method also includes computing reconstructed electrical signals for locations on a surface of interest within the patient&#39;s body based on the synchronized electrical data and geometry data. The geometry data represents locations of the EP electrodes, a location of the IMD electrode within the patient&#39;s body and the surface of interest.

RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.17/179,465, filed Feb. 19, 2021, and entitled USING IMPLANTABLE MEDICALDEVICES TO AUGMENT NONINVASIVE CARDIAC MAPPING, which is incorporatedherein by reference in its entirety.

TECHNICAL FIELD

This disclosure relates to using implantable medical devices to augmentnoninvasive cardiac mapping.

BACKGROUND

Electrocardiographic imaging (ECGI) is a noninvasive multi-lead ECG-typeimaging tool that combines noninvasive electrical measurements withthree-dimensional geometry of the heart and torso to reconstructelectrical signal onto the heart or another surface. Mathematically,this is performed by solving the inverse problem. However, the inversesolution is ill-posed such that inaccuracies in the measured electricalsignals can result in significant errors.

SUMMARY

This disclosure relates to using implantable medical devices to augmentcardiac mapping, which may include noninvasive and/or invasive cardiacmapping.

As one example, a method includes establishing a communications linkbetween a cardiac monitoring system and an implantable medical device(IMD). The IMD includes one or more IMD electrodes. IMD electrical datais received at the monitoring system via the communications link. TheIMD electrical data is synchronized with electrical measurement data toprovide synchronized electrical data based on timing of asynchronization signal sensed by an IMD electrode and/orelectrophysiology electrodes. The method also includes computingreconstructed electrical signals for locations on at least one surfaceof interest within the patient's body based on the synchronizedelectrical data and geometry data. The geometry data may representlocations of the electrophysiology electrodes, a location of the IMDelectrode within the patient's body and the surface of interest.

As another example, a system includes an implantable medical device(IMD) comprising an IMD electrode or electrodes adapted to be positionedwithin a patient's body. The IMD includes circuitry to receive andinterpret IMD electrical data sensed by an IMD electrode or series ofelectrodes. In some examples, the IMD uses these electrical signals todetermine whether therapeutic pulses or shocks are require in order tomanage the patient's rhythm. Additionally, or alternatively, the IMD mayalso be used as a monitoring device to store electrical signals forlater interpretation by a physician. The system also includes amonitoring system. The monitoring system includes non-transitory memoryand a processor. The memory may store the IMD electrical data,monitoring electrical data and geometry data. The monitoring electricaldata may represent signals measured by monitoring electrodes, which mayinclude body surface electrodes distributed on a surface of thepatient's body and/or one or more invasive electrodes within thepatient's body. The processor is coupled to the memory to access dataand instructions stored in the memory. The instructions may beprogrammed to establish a communications link between the monitoringsystem and the IMD and receive the IMD electrical data through thecommunications link. The instructions also synchronize the IMDelectrical data and the monitoring electrical data to providesynchronized electrical data based on timing of a synchronization signalsensed by the IMD electrode and/or the monitoring electrodes.Reconstructed electrical signals can be reconstructed for locationsresiding on a surface of interest based on the synchronized electricaldata and the geometry data. In another example, the monitoringelectrical data may include electrical measurement data from an invasiveelectroanatomic mapping system that may be combined with the informationfrom the IMD to further refine the electrical maps.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an example system that includes an implantable medicaldevice and electrophysiology monitoring system.

FIG. 2 depicts an example of another system that includes an implantablemedical device, programmer and electrophysiology monitoring system.

FIG. 3 depicts an example of a reconstruction engine.

FIG. 4 depicts an example of an implantable medical device that includesone or more leads.

FIG. 5 depicts an example of a leadless implantable medical device.

FIG. 6 depicts an example of an implantable medical device having leadsimplanted in or on a patient's heart.

FIG. 7 depicts an example of a sensor array.

FIG. 8 depicts an example of part of an image that includes animplantable medical device implanted within a patient's body.

FIG. 9 depicts an example of a sensing vector that may be sensed usingan implantable medical device.

FIG. 10 depicts an example of another sensing vector that may be sensedusing an implantable medical device.

FIG. 11 depicts an example of signals corresponding to the sensingvectors of FIGS. 9 and 10 .

FIG. 12 is a flow diagram depicting an example of a method of using animplantable medical device to augment electrophysiology mapping.

DETAILED DESCRIPTION

This disclosure relates to using implantable medical devices to augmentelectrophysiology mapping. An example system includes an implantablemedical device (IMD) and an electrophysiology monitoring system. Theimplantable medical device includes one or more IMD electrodes adaptedto be positioned at a location within a patient's body. The implantablemedical device including circuitry (e.g., analog and/or digitalcircuitry) to provide IMD electrical data based on an electrical signalsensed by the IMD electrode and to deliver a stimulus signal through theIMD electrode.

The monitoring system may be implemented as a computer system thatincludes non-transitory memory to store data, which may include IMDelectrical data from the IMD and electrophysiology (EP) electrical dataand geometry data. The EP electrical data may include noninvasiveelectrical measurement data representing noninvasive electrical activitymeasured noninvasively from surface locations on the patient's body.Additionally or alternatively, the EP electrical data may includeinvasive electrical measurement data representing electrical activitymeasured noninvasively within the patient's body. The geometry data mayrepresent the EP measurement locations, the IMD sensing location(s) aswell patient anatomy in three-dimensional space. The monitoring systemalso includes a processor coupled to the memory to access the data andinstructions stored in the memory to perform functions disclosed herein.For example, the instructions are programmed to establish acommunications link between the processor and the implantable medicaldevice. The communications link may be a direct link or an indirect linkthrough another device, such as a programmer, and may be bidirectional.

The processor is also programmed to determine timing of asynchronization signal as sensed by at least one electrode of the IMDand/or at least some EP electrodes, which are reflected in the EPelectrical data. The synchronization signal may be provided by one ormore electrodes at a location within a patient's body (e.g., by the IMDelectrode) and/or an EP measurement location (e.g., by a body surfaceelectrode or an invasive electrode). An EP map may be determined forrespective locations residing on a surface (or surfaces) of interestbased on the IMD electrical data, the EP electrical data (e.g.,noninvasive and/or invasive electrical measurements), the geometry dataand the timing of the synchronization signal.

In some examples, the IMD electrical data and geometry data associatedwith the IMD electrode(s) may be used to determine one or more boundaryconditions. The boundary condition may be used by the reconstructionengine to constrain an inverse solution that is utilized to reconstructthe electrical signal on the cardiac envelope.

Additionally, or alternatively, the monitoring system may be programmedto control an impedance measurement method in which impedance ismeasured between the IMD electrode(s) and EP electrodes. For example theimpedance may be measured based on one more signals (e.g., subthresholdor suprathreshold signals) that are generated at the IMD electrode(s)and/or EP electrodes. The impedance measurements may be used tocharacterize the conductivity of the tissue and fluids located withinthe patient's body between the IMD electrode(s) and EP electrodes on thebody surface. The processor further may be programmed to generate orupdate model data representing an anatomic model, which is used tocompute one or more EP maps on the surface of interest.

In view of the foregoing, by leveraging information from the IMD, theaccuracy of reconstructed electrical signals themselves can be improvedas well as improved EP mapping functions. For example, concurrent localand global assessments of cardiac tissue may be provided in a single EPmap. Moreover, the bidirectional link between the IMD and the monitoringsystem enable closed loop control that can achieve new sensing paradigmsin which signals usually measured by mapping catheters may be replicatedand integrated into the electrical measurements data without requiringuse of an actual catheter. Because, in some examples, the systems andmethods may be implemented without use of an electrophysiology (EP)catheter the likelihood of inadvertently dislodging the IMD or its leadsis mitigated.

FIG. 1 depicts an example of a system 10 for augmenting EP mapping. Thesystem 10 includes an implantable medical device (IMD) 12 and amonitoring system 14 that are configured to communicate over acommunication link 16. The communication link 16 may include one or morewireless and/or physical connections (e.g., electrical conductors,optical fibers). Useful examples of the implantable medical deviceinclude an implantable cardioverter-defibrillator, a pacemaker or aventricular assist device. Some commercial examples IMDs that may beused as the IMD 12 include implantable cardioverter-defibrillator fromMedtronic plc, such as including the Visia ICD system, the Evera ICD,the Crome system and the Cobalt System. Commercial examples ofpacemakers and pacing systems that may be used to implement the IMD 12include the Azure pacemaker, the Advisa pacing system, the Adaptapacemaker and any of the Micra transcatheter pacing systems, which areavailable from Medtronic plc. In other examples, different pacingsystems may be used as the IMD 12.

In the example of FIG. 1 , the IMD 12 includes a communications module18 configured to communicate data (e.g., IMD data and instructions)through the communication link 16. For example, the communicationsmodule 18 can communicate through the link 16 with one or more devicesincluding the monitoring system 14. The IMD 12 also includes one or moreIMD electrodes 20. The electrodes may be mounted to a housing thatcontains the IMD 12. Additionally, or alternatively, the electrodes 20may be mounted to one or more leads that may extend from the housing ofthe IMD. The number and placement of electrodes can vary depending uponthe type of IMD that is being utilized for a given patient. In someexamples, one or more IMD may be used concurrently for a given patient.

The IMD 12 also includes an electrode interface 22 having respectiveinputs coupled to each of the electrodes 20. The electrode interface 22may include a sensing module 24 and a signal generator 26. For example,the sensing module 24 includes circuitry configured to measureelectrical signals received at the electrodes 20. The electrodeinterface 22 thus can include analog or digital circuitry configured toreceive, amplify and store the measured electrical signals, in memory28. For example, a processor 30 is coupled to the electrode interface 22to receive the electrical measurement data from the interface and storethe data in the memory 28 as IMD electrical measurement data.

The processor 30 may include any one or more of a microprocessor, acontroller, a digital signal processor (DSP), an application specificintegrated circuit (ASIC), a field-programmable gate array (FPGA), orequivalent discrete or integrated logic circuitry. In some examples,processor 30 may include multiple components, such as any combination ofone or more microprocessors, one or more controllers, one or more DSPs,one or more ASICs, or one or more FPGAs, as well as other discrete orintegrated logic circuitry. The term “processor” “processor module” or“processing circuitry” may generally refer to any of the foregoing logiccircuitry, alone or in combination with other logic circuitry, or anyother equivalent circuitry.

The signal generator 26 includes circuitry configured to deliver anelectrical signal to one or more respective IMD electrodes 20 based onelectrical parameters defined for the signal (e.g., pulse amplitude,pulse duration and frequency). The electrical signal may be a stimulussignal that may be subthreshold or super threshold. As used herein, the“subthreshold” refers to a signal that is sufficiently large to bemeasurable by one or more electrodes above baseline noise that isdetected by such electrodes, but that is not so large as to stimulatecardiac conduction (i.e., trigger an action potential to pace theheart). In contrast, suprathreshold refers to a signal that issufficient to stimulate cardiac conduction. In an example, the signalgenerator 26 may provide a signal to one or more of the electrodes 20 toperform pacing. For example, the processor 30 is programmed to controlthe signal generator to provide the electrical stimulus signal to one ormore electrodes such as to implement cardioversion, pacing ordefibrillation.

In some examples, the processor is configured to monitor the measurementsignals from the sensing module 24 and to control the signal generator26 to provide a suprathreshold stimulus signal responsive to the sensedmeasurement signals. Thus the IMD 12 may be implemented as aself-contained system such as implantable within the patient's body sothat the one or more electrodes are provided at desired locationsaccording to the type of stimulus to be provided to the patient's heart,such as to perform cardioversion and/or defibrillation.

The monitoring system 14 includes a communications module 32 that isconfigured to communicate with the implantable medical device 12 throughthe communication link 16. As described, the communication link 16 maybe direct communication with the implantable medical device or may be anindirect communication to one or more other devices (not shown). Thecommunications module 32 may include communications circuitry configuredto communicate using one or more forms of communication.

The monitoring system 14 also includes an electrode interface 34 that iscoupled to EP electrodes 36. In one example, the electrode interface 34may be coupled to an arrangement of EP electrodes 36 through respectiveelectrically conductive leads. In other examples, the EP electrodes maybe coupled to the electrode interface 34 through other forms ofcommunication (e.g., optical fiber or wireless leads). In an example,the EP electrodes are implemented as body surface electrodes to bedistributed non-invasively across a patient's body surface. In anadditional or alternative example, the EP electrodes are implemented aselectrodes configured for invasively measuring electrophysiologysignals, such as mounted to a catheter or other instrument that ismoveable within a patient's body.

The electrode interface 34 includes a sensing module 38 having circuitry(e.g., amplifier and/or filters) configured to receive signals measuredby the respective EP electrodes 36 and provide corresponding electricalmeasurement signals. The monitoring system 14 may also include aprocessor 40. The processor 40 may be similar in design and operation tothe processor 30 described above. The processor 40 is configured toexecute instructions to perform various control and processing functionsdisclosed herein (e.g., executable functions 50, 52, 60, 70 and 64).

In an example, the processor 40 includes a signal processing function toprocess the received measurement signals from the EP electrodes 36 andconvert the signals to corresponding body surface electrical data (EPdata 42). Alternatively, the electrode interface 34 may be configuredconvert the measurement signals to respective EP data 42. The signalprocessor 40 may be implemented as hardware and/or software, such asincluding a digital signal processor and other processing circuitry toremove noise and convert the received signals into a desired format forthe EP data 42. This can include adding channel information, addingtimestamps, line noise removal or other signal processing functions thatmay be desired.

In some examples, the electrode interface 34 also includes a signalgenerator 44. The signal generator 44 includes circuitry configured togenerate one or more signals that are supplied to respective EPelectrodes 36. For example, the signal generator 44 may generate a pulseor other types of signals to one or more of the EP electrodes 36 thatmay be detected by other EP electrodes and/or the IMD electrode(s) 20.

As described above, the monitoring system 14 may receive IMD electricaldata from the IMD 12 (e.g., as encoded data) through the communicationslink 16. The communications module 32 can decode the signal and extractthe IMD data and store such data in memory data as IMD electrical data46. The EP data 42 and IMD data 46 collectively form electrical data 48that is stored in memory (e.g., local and/or remote memory) of themonitoring system 14. For example, the IMD electrical data 46 includesdata representing signals generated and/or measured by the IMDelectrodes 20. The IMD data 46 may also include an electrode identifierthat specifies which electrode the data is associated with and includelocal timing information for the IMD 12.

In the example of FIG. 1 , the monitoring system 14 also includes asynchronization function 50 such as may be implemented asmachine-readable instructions executable by a processor of themonitoring system. The synchronization function 50 may control one ormore signal generators 44 and 26 to generate a synchronization signalvia respective electrodes 20 or 36. The synchronization signal may be asubthreshold signal or a suprathreshold signal. In response to thesynchronization signal, one or both sensing modules 24 and 38 measureelectrical signals and provide electrical measurement signals that maybe stored in memory of the monitoring system as respective IMDelectrical data 46 and EP data 42, as described above.

The synchronization function 50 is programmed to synchronize the IMDelectrical data 46 and the EP data 42 based on a timing of thesynchronization signal that is sensed by one or more of the electrodes20 and 36 and provided as part of the electrical data. For example, thesynchronization functions are programmed to set a zero or other commonstart time for an identified feature (e.g., peak of the pulse, bottom ofthe pulse, rising edge, falling edge) of the synchronization pulse. Thezero or other start time thus is used to align the data in time so thatthe identified data feature is at the alignment time for each of themeasurement channels. Alternatively, a timing offset may be determinedfor each of the channels and utilized to adjust the timing of theelectrical data 46 and the EP data 42 according to the timing offset.

As a further example, the synchronization function 50 is programmed tocontrol the signal generator of the IMD 12 through the communicationslink 16 to generate the synchronization signal through one or more ofthe IMD electrodes 20. For example, the synchronization function 50issues synchronization control instructions through the communicationsmodule 32 that are communicated via the link 16 to the IMD 12. Thecommunications module 18 decodes the received signal and the processor30 is configured to execute the instructions and thereby control thesignal generator 26 to deliver the synchronization pulse to one or morerespective electrodes 20 responsive to the instructions. Thesynchronization function 50 further instructs the sensing module 38 tomeasure electrical activity by the EP electrodes 36 (e.g., on and/orwithin the patient's body) responsive to the synchronization signal(generated by electrodes 20). The sensing module 24 also may measuresignals from one or other IMD electrodes 20 to generate IMD data.

The synchronization function 50 further may control the signal processor40 to analyze the measured electrical activity data (e.g., stored at EPdata 42 and/or IMD data 46) to identify a feature of the synchronizationsignal reflected in the measured electrical signals corresponding to thestored electrical data 48. The identified feature can be any signal,such as signal morphology and/or timing, which may manifest in thesignals being measured by the electrodes 36 or derived from the measuredsignals (e.g., peak of the pulse, bottom of the pulse, rising edge,falling edge, frequency and the like). The synchronization function 50thus may utilize the identified feature to synchronize the IMD data 46with the EP data 42.

As another example, the synchronization function 50 is programmed tocontrol the signal generator 44 to generate a synchronization signal viaone or more of the EP electrodes 36. As described herein, the EPelectrodes 36 may include body surface electrodes for a non-invasive EPsystem and/or invasive electrodes for an invasive EP system. Thesynchronization function 50 may employ the communications module 32 toreceive IMD synchronization data via the communications link 16. The IMDsynchronization data thus may represent electrical signals measured byone or more respective IMD electrodes 20 responsive to thesynchronization signal generated by one or more of the EP electrodes 36.In some examples, the synchronization function 50 may provideinstructions to the IMD 12 such that the processor 30 activates signalgenerator 26 to measure electrical signals using one or more IMDelectrodes 20 during the synchronization signal that is generated on thebody surface. The received synchronization data may be stored as part ofthe IMD electrical data 46. The synchronization function 50 may employthe signal processor 40 to analyze the electrical activity of the IMDsynchronization data to identify a feature of the synchronization signalthat is reflected in the measured signal, as described above. Thesynchronization function thus synchronizes the IMD data 46 and the EPdata 42 based on the identified feature. The synchronized data may beanalyzed and further processed to augment or enhance the functions ofthe monitoring system. In some examples, the IMD data 46 or the EP data42 amplitude may be adjusted to a common scale (e.g., a normalizedscale) to facilitate analysis and processing of the synchronizedelectrical data 48.

For example, the synchronization function 50 can synchronize the IMDdata 46 and EP data 42 for a given time interval of the measuredelectrical signals. For subsequent intervals, the synchronizationfunction 50 may recompute the synchronization between the respectivesignals represented by the IMD data 46 and EP data 42 for the respectiveintervals. In some examples, the synchronization function 50 isprogrammed to periodically or intermittently generate a synchronizationsignal (e.g., internally via one or more of the IMD electrodes 20 and/orexternally via one or more of the EP electrodes 36) and align theelectrical data 42 and 46 to maintain accurate synchronization amongsuch data for subsequent analysis and reconstruction by thereconstruction engine 52. This is especially useful to ensure accuracyis sustained during lengthy electrophysiological studies.

The monitoring system 14 may also include a reconstruction engine 52(e.g., instructions) programmed to compute reconstructed electricalsignals for locations on a surface of interest within the patient'sbody. In one example, the, the reconstruction engine 52 computes thereconstructed signals (e.g., electrical potentials) on the surface ofinterest by executing instructions (an algorithm) to combined electricalsignal spatially and temporally based on geometry data 54 and theelectrical data (e.g., EP data 42 and IMD data 46). In another example,the reconstruction engine 52 computes the reconstructed signals (e.g.,electrical potentials) on the surface of interest by executinginstructions (an algorithm) to solve the inverse problem based ongeometry data 54 and the synchronized electrical data (e.g., EP data 42that has been synchronized with IMD data 46). Examples of inversealgorithms that can be implemented by the reconstruction engine 52include those disclosed in U.S. Pat. Nos. 6,772,004, 7,983,743 and9,980,660, each of which is incorporated herein by reference. Thereconstruction engine 52 can calculate the reconstructed electricalsignals on the surface of interest for one or more surfaces of interestover one or more time intervals. The time interval(s) may be selectedthrough a user interface 60 in response to a user input entered by auser device 62 (e.g., mouse, keyboard, touchscreen interface, gestureinterface or the like).

For example, the reconstruction engine 52 is programmed to calculate atransfer matrix based on the geometry data 54 and the synchronizedelectrical data. The reconstruction engine 52 further may employ aregularization technique to estimate values for the reconstructedelectrical signals on the surface of interest, which is defined by thegeometry data 54.

In the example of FIG. 1 , the geometry data 54 includes EP data 56representing three-dimensional locations of the EP electrodes 36distributed across a patient's body. The geometry data also includes IMDdata 58 representing locations of the IMD electrodes 20 within thepatient's body. In some examples, the body geometry data and the IMDgeometry data are derived from a common source (e.g., three-dimensionalimage set or a navigation system), which helps to further improve theaccuracy of the relative three-dimensional position of the electrodes 20and 36 as well as the resulting reconstructed signals. The geometry data54 also includes data representing the surface (or surfaces) of interestin three-dimensional space. For example, the surface of interest is acardiac envelope, such as an epicardial surface, an endocardial surface,a combination of epicardial and endocardial surfaces of the patient'sheart or other three-dimensional geometrical surface (e.g., a sphere).In some examples, the geometry data represents the surfaces of interestas three-dimensional data describing a surface on to which reconstructedsignals are computed (by engine 52) and one or more surfaces whereinvasive measurements are made (e.g., by the IMD electrodes and/orelectrodes of an invasive EP monitoring system).

As an example, the geometry data 54 is derived from image data acquiredfor the patient and includes spatial coordinates for the patient's heartand the electrodes 20 and 36. Image data can be acquired using nearlyany imaging modality based on which a corresponding representation canbe constructed, such as described herein. Examples of imaging modalitiesinclude ultrasound, computed tomography (CT), 3D Rotational angiography(3DRA), magnetic resonance imaging (MRI), x-ray, 3D ultrasound, positronemission tomography (PET), fluoroscopy and the like. Such imaging may beperformed concurrently with recording the electrical activity that isutilized to generate the sensed electrical data 40 or the imaging can beperformed separately (e.g., before or after the measurement data hasbeen acquired). The location for each of the electrodes 20 and 36 can beprovided in the geometry data 54 by acquiring the image while theelectrodes are disposed on the patient and identifying the electrodelocations in a coordinate system through appropriate image processing,including extraction and segmentation. The resulting segmented imagedata can be converted into a two-dimensional or three-dimensionalgraphical representation that includes the volume of interest for thepatient. Appropriate anatomical or other landmarks, including locationsfor the IMD 12, as well as the electrodes 20 and 36, can be identifiedin the geometry data 38 to facilitate spatial registration of theelectrical data 48. The identification of such landmarks can be donemanually (e.g., by a person via image editing software) or automatically(e.g., via image processing techniques).

In some examples, the geometry data 38 represent anatomic and electrodegeometry as a mathematical model, which can be a generic model or amodel that has been constructed based on image data obtained for thepatient. Alternatively, or additionally, the geometry data 38 caninclude a generic or custom representation (e.g., a model) of the heart,which may not be the patient's own heart. In such a case, the sensedelectrical data 40 can be mapped (e.g., via registration) to therepresentation of the organ according to identified anatomicallandmarks.

As a further example, the reconstruction engine 52 is programmed tocalibrate the heart-torso model to take into account inhomogeneity ofthe patient's body between the heart and the surface electrodelocations. For example, the monitoring system 14 may be programmed tocontrol the IMD 12 to generate a calibration signal (e.g., an electricalsignal) by one or more of the IMD electrodes 20. In other examples, themonitoring system 14 can provide instructions to the signal generator 44to control one or more of the EP electrodes 36 to generate thecalibration signal. The reconstruction engine 52 or another method(e.g., signal processor 40) is programmed to determine impedance of apatient's body between the respective IMD electrodes 20 and respectivesurface electrodes 36 responsive to the calibration signal. For example,variations in the amplitude of signals generated by the IMD electrodes20 and measured by the body surface electrodes 36 can provideinformation relative to variations in transthoracic impedance. Frequencyof the calibration signals may also be varied as part of determiningtransthoracic impedance between the respective electrodes 20 and 36. Forexample, the impedance can be utilized to generate an impedance map ofthe patient's body. The impedance data thus may be used to calibratemodel data that characterizes inhomogeneity of a patient's body betweenthe heart and the surface electrode locations based on the impedance.User interface 60 may be used in some examples to selectively employ theimpedance information to calibrate the model data accordingly. Forexample, inhomogeneities may be selectively applied to the part of aheart-torso model that represents conductivity of the patient's body,such that some of the volume-body conductor may be represented as ahomogeneous conductor and other portions of the volume-body conductorrepresented by the model may reflect inhomogeneities. The reconstructionengine 52 thus may compute reconstructed electrical signals on thesurface of interest using the calibrated model data.

In another example, additionally or alternatively to the featuresdescribed herein, the reconstruction engine 52 further may be programmedto determine one or more boundary conditions based on the IMD data 46and 58. The boundary condition may be applied automatically or beselectively applied in response to a user input (e.g., through userinterface 60). The reconstruction engine 52 further may be programmed tocompute reconstructed electrical signals on the surface of interestbased on the synchronized electrical data 48, including signals measuredby the IMD electrode 20 and the EP electrodes 36, the geometry data 54in which the reconstruction engine imposes the boundary conditions torestrain the computations being implemented to determine thereconstruction electrical signals.

The monitoring system 14 also includes a map generator 64 that isprogrammed to generate an EP map that can be rendered on a display 68 tographically visualize the reconstructed electrical signal on the surfaceof interest. As disclosed herein, the surface of interest may be anepicardial surface, an endocardial surface, or a combination of anepicardial or endocardial surfaces. Additionally, the surface ofinterest can be a cardiac envelope, such as a surface residing betweenthe center of a patient's heart and the body surface where theelectrodes are positioned. The surface of interest may encompass theentire cardiac surface or one or more surface regions (epicardial orendocardial) such as described herein.

The map generator 64 thus provides output data 66 that may be providedto the display 68 to visualize one or more electrocardiographic maps aswell as other electrical information derived from the reconstructedelectrical signals. For example, the map generator 64 is programmed togenerate an EP map based on the reconstructed signals (generated byreconstruction engine) and invasively measured electrical information(e.g., from the IMD and/or an invasive EP monitoring system). Byincluding reconstructed electrical signals (derived from non-invasivemeasurements) and actual signals (measured invasively) in a combined EPmap, the combined EP map concurrently provides respective global andlocal assessments in the EP map. Additionally, or alternatively, thereconstructed electrical signal on surface of interest may further beenhanced through electrical signals acquired concurrently by invasivemeasurements, including by the IMD and/or invasive electroanatomicmapping systems.

In some examples, the calibration pulses can be used in a similar mannerto synchronize data acquired invasively by the IMD and an invasive EPmonitoring system. The reconstruction engine 52 thus may temporally andspatially combine the synchronized invasive measurements from the IMDand the invasive EP monitoring system into an EP map of correspondingelectrical signals based on the respective IMD electrical data, the EPelectrical data and corresponding geometry data representing spatiallywhere the invasive measurements are acquired. The map generator 64 isprogrammed to generate a visualization based on the EP map of thecorresponding invasive electrical signals.

As a further example, the monitoring system 14 may include a virtualphysiological (EP) study function 70. The virtual EP study function 70is a set of executable instructions programmed to enable a user toperform an EP study for a patient without requiring a catheter or otherprobe to be physically inserted within the heart. Instead, the virtualEP study function 70 leverages communications link 16 between analready-implanted IMD 12 and the monitoring system 14 and the knownspatial registration (e.g., in the geometry data) and electricalregistration (e.g., by synchronization function 50 synchronizing theelectrical data 48) to perform the study.

As an example, the virtual EP study function 70 is programmed to controlthe IMD 12 via the communications link 16 to generate a stimulus signalvia one or more of the IMD electrodes 20. For example, after decodingthe signal communicated through the link 16, the communications module18 may provide the processor 30 with decoded instructions from thefunction 70. The processor 30 executes the instructions and controls thesignal generator 26. In response, the signal generator 26 may provide arespective stimulus signal (voltage or current) supplied to one or moreof the IMD electrodes 20 (e.g., a single pulse from a single electrodeor a potential between a pair of electrodes).

For example, a stimulus may be a suprathreshold signal to stimulate aregion of the heart where respective electrodes have been fixed. Becausethe position of each of the electrodes 20 is known and stored in the IMDgeometry data 58, the EP study function 70 can provide differentstimulus signals (e.g., having different signal parameters such asamplitude, pulse width and, if needed, frequency). The resulting cardiacsignals that propagate across the heart responsive to each such stimulussignals may be recorded as electrical data 48. For example, the cardiacsignals responsive to the stimulus signal may be measured invasively byone or more other implanted electrodes 20 as well as by measurements bythe EP electrodes 36. Signals measured by IMD electrodes may be storedin memory 28 as IMD data and be communicated to the monitoring systemvia the link 16, as described herein.

In some examples, the stimulus signal may be utilized by thesynchronization function 50 (as a synchronization signal) to synchronizethe signals during the virtual EP studies that are being implemented.The measured electrical activity may be stored in memory as electricaldata 48, including both IMD data 46 and EP data 42 responsive to thestimulus signal that is generated. The virtual EP study function 70 thenmay employ the reconstruction engine 52 to compute reconstructedelectrical signals on the surface of interest based on the measuredelectrical activity (e.g., synchronized electrical data 48) and thegeometry data 58, as described herein.

As a further example, the stimulus signals may be used to refine themodels and/or to assess the electrical characteristics of certainregions, which may be the same or different region from where stimulussignals are applied. For example, pacing from multiple locations andwith varying rates and frequencies (e.g., extrasystolic beats) can helpto define the electrical properties of local tissues, such as includingconduction velocities, refractory periods, and the like. Electricalsignals reconstructed across the surface of interest, including multiplechambers or the entire heart, which are reconstructed (by reconstructionengine 52) responsive to the stimulus signals, further may provide aglobal assessment of the stimulus on cardiac tissue. For example, theglobal assessment may show effects of such stimulus at one or moreregions that are different from where the stimulus signals are appliedor across the entire surface of the heart.

In some examples, where additional IMD electrodes 20 and/or otherinvasive electrodes are positioned to measure the cardiac response tothe stimulus signal, the surface of interest may include both anendocardial surface as well as an epicardial surface. The map generator64 may in turn generate electrocardiographic map that is provided asoutput data 66 and rendered on the display 68. Additionally, in someexamples, the virtual EP study may use a user interface 60 to enable auser to trigger application of the stimulus signal through thecommunications link 16 in response to a user input made with the userdevice 62. In one example, the user device may include a trigger orbutton in a form factor and configuration similar to the trigger or thestimulus control that is provided for an EP catheter.

By way of further example, the stimulus signal may be used to generate aseries of cardiac maps (based on reconstructed electrical signals on thesurface of interest during a series of stimulus signals) that areevaluated to determine control parameters, such as pacing parameters foruse by the IMD to perform pacing (e.g., cardiac resynchronizationtherapy (CRT)) or another forms of cardiac rhythm therapy (e.g.,cardioversion and/or defibrillation). For example, the study function 70may control the IMD 12 via the link 16 to provide a series of differentstimulus signals from selected electrodes 20 and/or having differentstimulation parameters. Examples of some stimulus signals that may beused for ventricular pacing stimulus and sensing, which may varydepending on the location and type of electrodes, are shown in thefollowing table. In the example table, the IMD includes left ventricularelectrodes LVi (where i is an electrode identifier specifying respectiveelectrode), a right ventricular ring electrode (RV Ring) and a rightventricular tip electrode (RV Tip). Other numbers and types ofelectrodes may be used in any combination, which may be controlled bythe EP study function 70 to provide various stimulus signals and tosense cardiac electrical activity endocardially.

RV Tip to RV Ring LV2 to LV1 LV3 to LV2 LV1 to RV Coil LV2 to LV3 LV3 toLV4 LV1 to LV2 LV2 to LV4 LV4 to RV Coil LV1 to LV3 LV3 to RV Coil LV4to LV1 LV1 to LV4 LV3 to LV1 LV4 to LV2 LV2 to RV Coil LV4 to LV3

In some examples, the reconstruction engine 52 may be configured, inresponse to the user input via the user interface 60, to reconstruct theelectrical activity on the surface of interest based on the EPelectrical data 42 but in the absence of using the IMD data 46. Then, inresponse to a further user input via the interface 60 or as part of anautomated workflow, the reconstruction engine 52 may reconstructelectrical activity on the surface of interest utilizing the same EPdata 42 and synchronized IMD data 46 so that the input cardiacinformation from the IMD 12 can augment and correct deficiencies. A usermay use both maps to identify differences based on the additionalintracardiac measurements or the maps may be combined into a comparativegraphical map that is provided as output data 66 to the display 68. Insome examples, weighting and scaling of cardiac signals can be appliedto increase the contribution of the intracardiac measurement withrespect to reconstructed electrical activity generated from body surfaceelectrical measurements. Additionally, the intracardiac measurements byone or more electrodes 20 may be registered (spatially and temporally)with the reconstructed electrical data to provide additional informationboth epicardially and endocardially, for example.

FIG. 2 depicts another example system that includes an IMD 12 to augmenta noninvasive cardiac monitoring system 14. The system 80 in FIG. 2 isidentical to the system of FIG. 1 . The same reference numbers are usedin FIG. 2 to refer to features and components described herein withrespect to FIG. 1 and new reference numbers refer to features introducedin FIG. 2 . In FIG. 2 , the communications link 16 includes multiplelink portions, shown as a first link 82 and a second link 84. The firstlink 82 is a communication link between the monitoring system 14 and aprogrammer 86. The second link 84 is between the programmer 86 and theIMD 12.

The communications between the IMD 12 and the monitoring system 14 passthrough the programmer 86. In one example, the programmer may operate ina passive manner and receive a signal via one of the links 82, 84,decode and re-encode the signal and send it out over the other link. Inanother example, the programmer may operate more actively by analyzing(or interpreting) the decoded data. The programmer may generate its owninstructions and data based on the decoded data received via a link 82,84 and/or re-package the data in a new container that is formatted(e.g., according to a predefined schema) for the recipient (the IMD 12or system 14).

The programmer 86 includes a communications module 88 configured tocommunicate with the communications module 32 through bi-directionallink 82 and to communicate with the IMD communications module 18 throughbidirectional link 84. The programmer also includes a processor 90,memory 92, a user interface 94 and a display 96. For example, thecommunications module 88 may include multiple communications interfaces,including at least one for communication with the IMD 12 and another forcommunication with the monitoring system 14. The physical layerimplementation for each interface depends on the physical layerimplemented by each link 82 and 84.

In an example, the communication link 84 between the programmer 86 andIMD 12 is a wireless link (e.g., Bluetooth, WiFi, cellular data or thelike). The communication link 82 between the monitoring system 14 andthe programmer 86 may be a wireless link or a physical link (e.g.,electrically conductive wires or optical fiber) or it may include morethan one type of physical layer.

As a further example, the communications module 32 is configured tocommunicate with the programmer 86 via the link 82. The communicationsmodule 18 of the IMD 12 is likewise configured to communicate with theprogrammer 86 through the link 84. Thus, the communications module 88may include multiple communication interfaces, such as a wirelessinterface to communicate over the link 84 and another interface tocommunicate over link 82 with the communications module 32.

In some examples, programmer 86 may be a handheld device or amicroprocessor-based home monitor or bedside programming device. A user,such as a physician, technician, nurse or other clinician, may interactwith programmer 86 to communicate with IMD 12. For example, the user mayinteract with programmer 86 via user interface 94 to retrieve currentlyprogrammed operating parameters, current physiological data and/orhistorical physiological data collected by IMD 12, or device-relateddiagnostic information from IMD 12. A user may interact with programmer86 to program IMD 12, e.g., select values for operating parameters ofthe IMD.

A user may also interact with the programmer to establish thecommunication link 82 with the monitoring system 14 and to enable themonitoring system 14 to implement control and programming of the IMD.When the monitoring system is connected with the programmer 86 via thelink 82, a user may employ the user interface 60 to take over operationof the programmer 86 for controlling operation of and/or programming theIMD 12. For example, a user interacting with the monitoring system 14via user interface 60 can initiate the virtual EP function 70 to performan EP study, as described herein. A user can also perform otherfunctions via the user interface 60, such as including a CRToptimization procedure performed by IMD 12 automatically orsemi-automatically, to establish data for closed-loop optimization ofCRT control parameters. The user may evaluate the output data on thedisplay (e.g., electrocardiographic maps) to determine CRT controlparameters for programming the IMD 12.

In some examples, programmer 86 may include a programming head (notshown) that is placed proximate to the patient's body near the IMD 12implant site to enable communications via link 84. In other examples,programmer 86 and IMD 12 may be configured to communicate using adistance telemetry algorithm and circuitry that does not require the useof a programming head and does not require user intervention to maintaina communication link.

In some examples, the link 82 may be a communications network (e.g.,local area network) to which the communications module 88 is coupled forcommunicating data to and from the monitoring system 14. Additionally, aremote user further may access the programmer 86 and/or the monitoringsystem 14 via the network link from a remote computer or workstation toallow remote monitoring and management of IMD 12 and the monitoringsystem 14.

Additionally, the monitoring system 14 may retrieve historical data thathas been stored in the memory 92 of the programmer based on electricalsignals measured by the IMD 12 and provided to the programmer via thelink 84. For example, electrical signal measurements may be made by oneor more electrodes of the IMD 12 over multiple measurement intervalsover an extended period of time (e.g., days or weeks), and theelectrical data may be stored in the memory 92. The monitoring system 14may retrieve the data for displaying the measured signals and beconfigured to perform further analysis, which may include automaticanalysis by the signal processing function and/or analysis by a userbased on a visualization of the stored signals on a display.

By way of example, the IMD 12 may be programmed to store historicalelectrical data based on measured cardiac signals acquired by one ormore implanted leads 20 to represent electrical activity associated witha known cardiac event. The implanted leads of the IMD 12 may includeendocardial leads, epicardial leads or a combination of endocardial andepicardial leads. The locations of each lead and its respectiveelectrode(s) 20 are at known locations in the heart. The electricalmeasurement data for one or more cardiac events (e.g., one or morecardiac intervals) may be stored in memory of the IMD 12 responsive todetecting a respective cardiac event. Examples of recurring cardiacevents, which may be stored in the memory 28 of the IMD 12, includepremature ventricular contraction (PVC), acute coronary syndrome (ACS)and congenital long QT syndrome to name a few.

The reconstruction engine 52 of the monitoring system 14 thus canreconstruct electrical activity for a region or the entire heart basedon non-invasively measured electrical data, as described herein. Themonitoring system 14 can also receive the electrical measurement datafor a respective cardiac event, as measured at one or more known cardiaclocations, through the link 82. The monitoring system 14 includesinstructions (e.g., program code) further configured to locate a regionor points in the reconstructed cardiac data corresponding to the one ormore known cardiac locations where the event was measured by the IMD 12.After the regions or points in the reconstructed electrograms arealigned spatially with respective location(s) where the IMD measured thecardiac event (e.g., PVC or other event), the monitoring system 14 isconfigured to compare the reconstructed electrical signals for anotherdetected instance of the cardiac event with the recorded electricalsignals for a prior instance of the event. Alternatively, a template maybe created (e.g., by the monitoring system 14 or programmer 86) based onthe recorded signal of the prior instance of the cardiac event, and thetemplate is compared with the reconstructed signals for the region orpoints corresponding to the recorded measurement locations. Thecomparison (a difference between the reconstructed and recorded signals)can be used by monitoring system 14 to determine an accuracy of thereconstructed electrical signals.

In an example, the monitoring system 14 is configured to adjust thereconstruction method (e.g. inverse solution) based on the comparison sothe reconstructed electrical signals better match the signals recordedby the IMD 12 for the event. For example, the adjustment can includeadjusting the reconstructed signals spatially to minimize a differencebetween the reconstructed signals and the signals recorded by the IMDfor the event. Alternatively or additionally, the locations ofreconstructed signals that correlate more highly with the recorded IMDsignals can be weighted more heavily in a transfer function used forsolving the inverse solution to reconstruct the electrical signals.

In a further example, activation time of cardiac signals at one or moreknown locations may be determined based on cardiac signals measured byone ore electrodes 20 of respective the implanted leads of the IMD 12.The monitoring system may use the activation time derived from thedirectly measured signals to improve a corresponding activation mapgenerated by the monitoring system based on reconstructed cardiacsignals (generated from non-invasively measured cardiac signals). Forexample, the monitoring system 14 is configured to compute a differencebetween the activation time for electrodes 20 of the IMD 12 and theactivation time for a set of cardiac nodes (nodes localized at or nearthe IMD electrode locations) for which the electrical signals have beenreconstructed. The monitoring system 14 can use the computed differencebetween respective activation times to augment (e.g., optimize) theactivation map. In one example the activation map augmentation includesthe monitoring system 14 assigning a greater weight to nodes that aretemporally and spatially synchronized (i.e., consistent) with respect tothe IMD electrodes 20 for which activation time has been determined. Inanother example, the activation time determined for electrodes 20 of theIMD 12 may be used as a boundary condition that is used by thereconstruction engine 52 for computing reconstructed electrical signalson the cardiac surface of interest (e.g., a region or the entire heart).In yet another example, the monitoring system 14 is configure tominimize (e.g., by implementing a least squares or other minimizationalgorithm) the difference between the activation time the IMD electrodes20 and the activation time for reconstructed cardiac signals.

As a further example, monitoring system 14 is configured to identifyprevious arrhythmogenic activity (an event) on or in the patient's heartbased on historical data recorded by the IMD 12. The identified activityor event may be used as a starting point for further analysis by themonitoring system 14 based on reconstructed electrical activity on acardiac envelope based on non-invasively acquired electricalmeasurements. For example, the monitoring system 14 may be configured torecord electrical data (EP data 42 and/or IMD data 46) and reconstructelectrical signals on a surface of interest that includes a region ofinterest where the arrhythmogenic activity was identified in response tocardiac electrical signals measured by the IMD electrodes 20.Additionally, or alternatively, the virtual EP study function 70 mayprovide instructions to the IMD to deliver one or more stimulus signalsto the region where the arrhythmogenic activity was identified or otherregions to observe local and/or global electrical activity for the heartas demonstrated in reconstructed electrical signals.

FIG. 3 depicts an example system 100 that includes a reconstructionengine to reconstruct electrical signals on a surface of interest, suchas described in example systems 10 and 80 of FIGS. 1 and 2 . The examplesystem 100 is described in the context of the reconstruction engine 52being programmed to employ a boundary element method as part of theinverse solution. It will be understood that the reconstruction enginecan be programmed to utilize other techniques for solving the inverseproblem. As one alternative example, the reconstruction engine 52 may beprogrammed to implement a meshless approach that uses the method offundamental solution such as disclosed in the above-incorporated U.S.Pat. No. 7,983,743.

The system 100 includes a reconstruction engine 52, which may be used asthe reconstruction engine in of FIGS. 1 and 2 . The reconstructionengine 52 can generate reconstructed electrical activity data 102 bycombining measured electrical data 48 and geometry data 54 and. In theexample of FIG. 3 , the reconstruction engine 52 is programmed toimplement an inverse method that is includes a transfer matrixcalculator 104 and regularization function 106.

The reconstruction engine 52 further is configured to impose boundarycondition data 108 on the computations implemented by the transfermatrix calculator 104. The values defined for each unit of the boundarycondition being imposed by the transfer matrix calculator 104 caninclude fixed or variable boundary condition parameters.

In some examples, the system 100 includes a boundary condition generator112 to generate the boundary condition data 108. The boundary conditiongenerator 112 includes a boundary condition analyzer 116 and a boundarycondition selector 118. The boundary condition analyzer 116 isprogrammed configured to analyze supplemental information, such as IMDinformation stored as part of the electrical data 48 and the geometrydata 54. For example, the analyzer 116 can evaluate each unit of data toascertain whether it represents a valid boundary condition (e.g., todetermine the efficacy of the supplemental information as a boundarycondition for the inverse method). The validity of a boundary conditioncan depend on the supplemental information, such as including its valueand/or associated location. The boundary condition selector 118 can beconfigured to select boundary conditions determined by the analyzer 116to be valid. Additionally, the boundary condition selector 118 can beconfigured to exclude the supplemental information if the analyzingindicates that the supplemental information provides an invalid boundarycondition for the inverse method. In some examples, the boundarycondition selector 118 is programmed to select which one or more IMDelectrodes will be used as boundary condition data 108 in response to auser input (e.g., via user interface 60).

As an example, the geometry data 54 further may include informationdescribing cardiac electrophysiology, which can include fiber angles andorientation of myocardial fibers between the endocardium and epicardium.The reconstruction engine 52 thus can be configured to estimate aconduction orientation for reconstructed signals on a cardiac envelope(e.g., epicardial surface) based on the based on the fiber angles andthickness of the cardiac tissue between respective endocardial andepicardial surfaces. Alternatively, the fiber angles may be determinedseparately and stored with the geometry data 54. The reconstructionengine 52 can also determine conduction velocities and delays based oncomparing temporally aligned recorded measurements by the IMD electrodes20 and reconstructed cardiac signals based on non-invasive measurements.For example, if the IMD electrodes 20 are on the endocardium and theECGI reconstruction is on the epicardium, the reconstruction engine 52can estimate electrical conduction velocities and cardiac fiber anglesbetween endocardial and epicardial surfaces that would result in aconduction delay, enabling the determination of a correction factor—atleast for regions localized in proximity of the known locations of theIMD electrodes. The reconstruction engine 52 thus can employ thecorrection factor (e.g., as well as fiber angle and thickness) forrespective locations on the epicardium to translate or map respectivereconstructed epicardial signals from the epicardium to correspondingendocardial locations. That is, the reconstruction engine 52 isconfigured to translate reconstructed ECGI map data to an endocardialsurface based on the fiber angle and conduction orientation. Acorresponding endocardial map for a surface (or surfaces) of interestmay then be generated (e.g., by map generator 64) from portions ofendocardial map that have been translated onto the endocardial surfaceby applying the correction factor and rendered on a display.

As a further example, the electrical activity measured by one or moreIMD electrodes (e.g., IMD electrical data 46) and informationrepresenting the three-dimensional spatial location of the respectiveIMD electrodes (e.g., IMD geometry data 58) may be used to provideboundary condition data 108. As described herein, for example, the IMDincludes one or more IMD electrodes (e.g., ring electrodes, plates, orcoils) that are attached within the patient's body at fixed locations,which may be known locations or locations that can be determined by alocalization system. For example, the electrode locations may bedetermined as spatial coordinates in 3D space. In some examples, the IMDelectrode locations are determined from 3D imaging modality that is usedto image patient's body as part of a process to provide geometry forbody surface electrodes (e.g., non-invasive EP electrodes 36) asdescribed herein. The IMD data, which is used as boundary condition data108, thus can represent endocardial and/or epicardial measurements ofelectrical signals (e.g., potentials) at respective known locations,including direct measurements acquired over time within the patient'sbody.

In some examples, the IMD data includes electrical signal measurementsrecorded over a long period of time and stored in memory (e.g., memoryof the IMD and/or programmer). The IMD data thus may be retrieved by themonitoring system 14 via the communication link for use by thereconstruction engine 52, as disclosed herein. In other examples, theIMD data that is used for the boundary condition data 108 includes IMDelectrical signal measurements acquired by the IMD during an EP study(e.g., in response to instructions from virtual EP study function 70).Because the relative position of the IMD electrodes and body surfaceelectrodes may be determined with high accuracy (e.g., from a common 3Dimage set), using IMD data as boundary conditions can improve accuracyof the reconstructed signals that are derived from noninvasive EPelectrical measurements.

For the example where the transfer matrix calculator 104 is programmedto use BEM (boundary element method), the calculator 104 may employ theboundary condition data 108 to produce an extended linear system that isconstrained by each one or more boundary conditions that is applied. Forexample, the IMD electrical data 46 and/or IMD geometry data 58 may beused to provide one or more intracardiac boundary conditions that arestored in the boundary condition data 108. The electrical data may beobtained from one or more IMD electrodes, as described herein, and thusmay be a single measurement or a series of measurements that change overtime. The transfer matrix calculator 104 can be programmed to compute anextended linear system in which the boundary condition data 108 has beenimposed, such as the following:

$\begin{matrix}{{\begin{bmatrix}A \\e_{i_{1}} \\ \vdots \\e_{i_{K}}\end{bmatrix}\begin{bmatrix}v_{E_{1}} \\ \vdots \\v_{E_{N}}\end{bmatrix}} = \begin{bmatrix}\phi_{B_{1}} \\ \vdots \\\phi_{B_{M}} \\{u_{E}}_{i1} \\ \vdots \\{u_{E}}_{iK}\end{bmatrix}} & {{Eq}.1}\end{matrix}$

-   -   where:        -   matrix A is of size M×N generated by BEM approach,        -   v_(E) ₁ represents the unknowns of potentials at heart            surface,        -   ϕ_(Bi) represents measured body surface potentials,        -   e_(i) _(K) represents unit 1×N vector with e(i_(K))=1, and        -   u_(E) _(ij) represents IMD electrical data (e.g., data 46 in            FIGS. 1 and 2 ) measured from the heart surface.

As an additional or alternative example, where a scar/lesion based of anboundary condition is also included in the boundary condition data 108,such as may be stored in the IMD geometry data 58 (e.g., derived fromimage data), the transfer matrix calculator 104 can be programmed tocompute an extended linear system in which each such boundary conditiondata has been imposed, such as the following formulation:

$\begin{matrix}{{\begin{bmatrix}A \\e_{i_{1}} \\ \vdots \\e_{i_{K}}\end{bmatrix}\begin{bmatrix}v_{E_{1}} \\ \vdots \\v_{E_{N}}\end{bmatrix}} = \begin{bmatrix}\phi_{B_{1}} \\ \vdots \\\phi_{B_{M}} \\0 \\ \vdots \\0\end{bmatrix}} & {{Eq}.2}\end{matrix}$

While in the example of Eq. 2, the boundary condition sets the voltagepotential at the known locations defined by the boundary condition tozero (e.g., 0 V), as mentioned other fixed low voltage values could beused in other examples. In still other examples, the boundary conditionsfor locations corresponding to the identified scar/lesion region in Eq.2 and/or the measured intracardiac locations of Eq. 1 may be expressedin bipolar measurement format, such as corresponding to measurementsbetween respective pairs of IMD electrodes 20. In such bipolar examples,the above Eqs. 1 and 2 would be modified to replace the extended e_(i)_(K) vector according to the following bipolar expression:

u(x _(si))−u(x _(sj))=0x _(si) ,x _(sj) ∈S⊂Ω scar/lesion  Eq. 3

Additionally, the systems and methods disclosed herein can assigndifferent weights on the scar/lesion prior to adjust its impactspatially on the system, based on a certainty of this kind of priorsupplemental information. For example, scar, lesion or other conductiondefects can be defined using methods described herein with respect tovirtual EP study function 70 or through local measurements of impedance.

The regularization function 106 is programmed to apply a regularizationtechnique to solve the unknown values of electrical activity on theenvelope of interest (e.g., V_(Ei) in Eqs. 1 and 2) from the transfermatrix computed by the calculator 104. As an example, the regularizationfunction 106 is programmed to implement Tikhonov regularization, such asdescribed U.S. Pat. No. 6,772,004. In another example, theregularization function is programmed to employ another regularizationtechnique, such as generalized minimum residual (GMRes) regularization,such as disclosed in U.S. Pat. No. 7,016,719, which is incorporatedherein by reference. Other regularization techniques (e.g., SingularValue Decomposition (SVD) or Truncated Singular Value Decomposition(TSVD), can also be applied, in addition to, or in lieu of, thetechniques mentioned above. The reconstruction engine 52 can in turnprovide the reconstructed electrical activity based on the regularizedmatrix.

In an additional or alternative example, the system 100 (part ofmonitoring system 14) may include a model generator 120 programmed togenerate model data 122 representing three-dimensional transthoracicimpedance (e.g., conductivity) of a patient's body between the patient'sheart and body surface (e.g., where body surface electrodes arepositioned). For example, the model generator 120 includes an impedancecalculator 124, which is implemented as instructions executed by acomputer processor in the system 100, programmed to calculate impedanceof the transthoracic cavity (throughout the body conductive volume)based on the electrical data 48 representing electrical signalmeasurements between one or more of the IMD electrodes 20 and bodysurface electrodes (e.g., electrodes distributed across the patientthorax). For example, the monitoring system 14 is configured to controlrespective signal generators 26 and 44 to apply fields (e.g., injectelectrical energy in the form of current or voltage) between respectivepairs of the electrodes 20, 36. The electrode pairs may be pairs of IMDelectrodes, pairs of body surface electrodes or pairs that include oneIMD electrode and one body surface electrode.

For example, volumetric impedance data further may be estimated and usedto model inhomogeneities of the transthoracic cavity that is implementedin a torso model used by the reconstruction engine 52 for solving theinverse problem when reconstructing signals as described herein. Forexample, the volumetric impedance data may be estimated from imagingdata and/or based on one or more transthoracic impedance measurements(e.g., measured between an invasive electrode and one or more bodysurface electrodes). In an example, the impedance data may include anintrathoracic impedance information as measured by between IMDelectrodes (e.g., between one or more leads within the heart and an ICDin the chest), such as based on thoracic fluid monitoring (e.g., byOptivol fluid status monitoring, available from Medtronic, Inc. ofMinneapolis, Minnesota).

In one example, the monitoring system controls one or more signalgenerators to apply a potential (or electrical current) between one ormore pairs of electrodes, namely one IMD electrode and one or more bodysurface electrodes. A response is measured at other electrodes as theapplied potential is delivered between the respective electrode pair.For example, the currents used are relatively small, below the thresholdat which they would cause functional stimulation (e.g., a fewmilli-Amperes of alternating current at a frequency of about 10-100kHz). Similar measurements can be made for current applied to eachelectrode pair.

The sensing modules 24, 38 are used to measure voltage responses acrossrespective electrode pairs and to record corresponding measuredelectrical signals that are stored in the EP data 42. The impedancecalculator 124 thus can compute an indication of impedance betweenrespective electrode pairs throughout the volume. The model generator120 can determine the conductivity of the transthoracic cavity based onthe determined impedance and associated geometry data 54. In an example,the model generator 120 uses the determined impedance data betweenelectrode pairs and geometry data to provide a three-dimensionalrepresentation of impedance characteristics for the transthoracic volumeof the patient (e.g., a voxelized impedance map).

As a further example, impedance calculator 124 may utilize an EquivalentSingle Dipole (ESD) metho to determine impedance of the body volume. ESDis an approach that can be employed to represent a potential ϕ generatedby a single dipole in an infinite homogeneous medium. The potential ϕcan be defined as follows:

$\begin{matrix}{{\phi\left( {x,r^{\prime},p} \right)} = {\frac{1}{4\pi g}\frac{p \cdot \left( {x - {r\prime}} \right)}{{❘{x - {r\prime}}❘}^{3}}}} & (1)\end{matrix}$

-   -   where g is the impedance, p is the dipole moment, r′ is the        dipole location, and x is the location of observation point.

For the example of a system (e.g., system 100) that includes bothnavigation and body surface mapping, as a user paces from a pair ofbipolar catheter leads inside body, a dipole is formed, with thelocation of the dipole moment p and the dipole location r′ given orretrieved from the system. Then for each of the observation point, basedon equation (1), the reconstructions engine is programmed to calculatean ideal potential at the observation point x, assuming impedance g is aconstant across all directions, comparing with the actual potentialmeasured at the same point, then we can derive a ratio of impedance.

For each one or more pacing sites with measurements across differentlocations, the same process can be applied to determine the relativeratio of impedance along different directions surrounding the pacinglocation. This process creates a spherical impedance correction matrixfor that pacing site. The same process above can then be applied tomultiple pacing sites covering regions of interest around the heart,with different spherical impedance correction matrices calculated ateach of the pacing sites.

For an example of an electrical dipole and boundary condition, given theelectrical dipole resides spatially within a closed surface T, withdipole location r′ and dipole moment p, then the electrical potentialmeasurements p(x) at spot X (e.g., electrode locations on the bodysurface) satisfies the following potential for the closed surface T:

$\begin{matrix}{{\phi_{T}\left( {x,r^{\prime},p} \right)} = {{\frac{1}{4\pi}{\oint_{\partial T}{{\phi_{T}(s)}{\frac{\partial\left( \frac{1}{r} \right)}{\partial\overset{\rightharpoonup}{n}} \cdot {ds}}}}} + {\frac{1}{4\pi g}\frac{p \cdot \left( {x - {r\prime}} \right)}{{❘{x - {r\prime}}❘}^{3}}}}} & (2)\end{matrix}$

For a system with both navigation and body surface mapping, as one pacesfrom a pair of bipolar catheter leads inside body, the dipole is formed,with the location of the dipole moment p and the dipole location r′given or retrieved from the system. Then for each of the observationpoint on body surface, based on equation (2), one can calculate theideal potential at the observation point x assuming impedance g is aconstant across all directions, comparing with the actual potentialmeasured at the same point, then we can derive a ratio of impedance.

For each of pacing sites with measurements on body surface acrossdifferent locations, the same process can be applied to get the relativeratio of impedance along different directions surrounding the pacinglocation. This creates a spherical impedance correction matrix for thatpacing site. The same process above can then be applied to multiplepacing sites covering regions of interest around the heart, withdifferent spherical impedance correction matrices calculated at each ofthe pacing sites. Fitting and interpolation of spherical impedancecorrection matrices can be done, to correct regions that were not pacedbut are to be mapped.

In some examples, the body is modeled as a uniform (homogeneous)isotropic volume conductor between the cardiac envelope and the bodysurface (e.g., like that used in a torso-tank experiment). In otherexamples, the body is modeled as a non-uniform (inhomogeneous)anisotropic volume conductor between the cardiac envelope and thelocations on the body surface where the electrodes are positioned. Themodel generator 120 thus may utilize the volumetric impedance data inthe model data 122 to provide a more accurate representation of theintracavity impedance variations (e.g., inhomogeneities) associated withthe corresponding anatomical structure of the patient. In this way,because the heart is surrounded by the kings, fat, bone and muscletissue, each of which has its own specific conductivity, the torso modeland transfer matrix can account for such inhomogeneities based onimpedance information (determined by impedance calculator 124).

As an example, the model generator 120 is further programmed tocalibrate the model data 122 to reflect the volumetric impedance data,namely, to represent impedance inhomogeneities within the transfermatrix, such as described herein. For example, the model generator 120is programmed to determine an indication of homogeneity (orinhomogeneity) as a value within the conductive volume betweenrespective pairs of the electrodes. Additionally, or alternatively, theimpedance inhomogeneity of the conductive media between any pair ofelectrodes can be determined in part from imaging data, such as CT orMRI images (e.g., represented as part of the geometry data 54). Theinhomogeneity (or homogeneity) thus may can be determined modelgenerator based on imaging data, signal measurements or a combination ofimaging data and signal measurements. The model generator 120 thus mayutilize the resulting indication of inhomogeneity and impedance data forthe conductive volume to calibrate (or generate) the model data, such asto represent the conductivity of the volume conductor between the IMDelectrodes and the body surface electrodes.

The transfer matrix calculator 104 may be programmed to compute atransfer matrix based on the electrical data 48, the geometry data 54,boundary condition data 108 and the model data 122. In some examples,the model data is generated based on an estimated homogeneous impedanceof the conductive volume. In other examples, the model data iscalibrated based on the impedance data determined by the impedancecalculator, as described above.

As an example, the following demonstrates the inverse problem forreconstructing electrical signals on a surface of interest with unipolarprior information.

$\left\{ \begin{matrix}{{\phi(x)} = {{\phi_{T}}_{}(x)}} & {{x \in \Gamma_{T}},{Dirichlet}} \\{\frac{\partial{\phi(x)}}{\partial\overset{\rightharpoonup}{n}} = 0} & {{x \in \Gamma_{T}},{Neumann}} \\{{\phi(y)} = {\phi_{C}(y)}} & {{x \in \Omega},{{catheter}{unipolar}}}\end{matrix} \right.$

As another example, the following demonstrates the inverse problem forreconstructing electrical signals on a surface of interest based onbipolar prior information

$\left\{ \begin{matrix}{{\phi(x)} = {\phi_{T}(x)}} & {{x \in \Gamma_{T}},{Dirichlet}} \\{\frac{\partial{\phi(x)}}{\partial\overset{\rightharpoonup}{n}} = 0} & {{x \in \Gamma_{T}},{Neumann}} \\{{{\phi\left( y_{i,1} \right)} - {\phi\left( y_{i,2} \right)}} = {{\phi_{C}\left( y_{i,1} \right)} - {\phi_{C}\left( y_{i,2} \right)}}} & {{\forall{\begin{pmatrix}{y_{i,1},} \\y_{i,2}\end{pmatrix} \in \Omega}},{{catheter}{bipolar}{pairs}}}\end{matrix} \right.$

By way of example, in the Method of Fundamental Solutions (MFS), one canexpress potentials at each location as follows:

${\phi(r)} = {a_{0} + {\sum\limits_{i}^{M}{a_{i}{f\left( r_{i} \right)}}}}$${{where}{f(r)}} = \frac{1}{4g\pi r}$ r = x − y

With the spherical impedance correction matrix described above, thecorrected impedance for each of the (x,y) pairs can be applied, forexample, by changing the impedance g from a constant value to bedirection dependent value, namely, impedance data determined by theimpedance calculator 124.

FIG. 4 depicts an example of an IMD 400, which may be used to implementthe IMD 12 of FIGS. 1 and 2 . The IMD 400 includes a housing 402 thatincludes the circuitry for performing the functions thereof. Forexample, the housing 402 includes a communications module processor,memory and an electrical interface. The housing 402 may also include oneor more electrodes 404 mounted on the exterior of the housing. The IMD400 also includes one or more leads 406 and 408 that extend from thehousing. There can be any number of one or more leads as part of the IMD400. The lead 406 includes electrodes 410, 412, 414, and 416 distributedalong the length of lead such as for implanting on or in a patient'sheart in contacting particular anatomical structures. The lead 408includes an electrode 420, but in other examples may include more thanone electrode. The electrodes 410, 412, 414, 416, 420 may be implementedas ring electrodes, coil electrodes or other shapes of electrodes thatmay be mounted along the leads.

In one example, the lead 406 may be a left ventricular lead and the lead408 may be a right ventricular lead. The combination of electrodesfurther may be used to sense signals that propagate between the anatomicregions in which the electrodes are located. For example, an electricalstimulus signal may be generated by a signal generator implemented inthe housing 402 and applied to one or more of the electrodes. Thepropagation of the signal and response may be sensed by one or more ofthe other electrodes. For example, the stimulus signal may be deliveredby an electrode in one chamber of the patient's heart (e.g., atrium orventricle) and sensed by an electrode in another chamber of thepatient's heart responsive to the stimulus.

FIG. 5 depicts another example of an IMD 500 that may be utilized in thesystems and methods described herein. The IMD 500 includes an elongatedbody 502 extending between spaced apart ends 504 and 506. The IMD 500includes one or more electrodes, demonstrated at 508 and 510 in theexample of FIG. 5 . The electrode 508 is demonstrated as a cylindricalring disposed around the body 502 of the IMD 500. There may be anynumber of one or more such ring electrodes disposed along the body atdifferent locations. The electrode 510 is an end cap electrode that isdisposed at the end 506. The IMD 500 is an example of the leadless IMD.Commercial examples of the leadless IMD include the Micra devicesavailable from Medtronic plc.

As a further example, FIG. 6 depicts an example of an IMD 600 in whichthe plurality of leads 602, 604 and 606 have been fixed within apatient's heart 610. Each of the leads includes one or more electrodes,such as described herein. Additionally, housing 612 of the IMD 600 mayinclude one or more electrodes 614. In the example of FIG. 6 , the leadsare mounted in the right atrium, right ventricle and left atrium. Theleads may be mounted in or on any parts of the heart, including one ormore endocardial leads having electrodes for sensing endocardialelectrical potentials.

FIG. 7 depicts one example of a sensor apparatus 700 that may beattached to a person's torso for noninvasively sensing body surfaceelectrical signals. The example sensor apparatus 700 may be configuredaccording to the embodiments disclosed in U.S. Pat. No. 9,655,561, whichis incorporated herein by reference. Other forms and arrangements ofelectrodes may be used in other examples, such as including the sensorapparatus disclosed in EP Patent No. 2352421.

The example sensor apparatus 10 is dimensioned and configured to beapplied to a torso of a patient (e.g., a human patient); however,different configurations can be utilized depending on the patient (e.g.,could be human or other animal) and the particular type ofelectrophysiology to be performed. The sensor apparatus 700 can come ina plurality of sizes to accommodate a range of patient's sizes and bodytypes.

The sensor apparatus 700 may include one or more substrate layers 712that are formed of a flexible material. The substrate layer 712 providesan electrode-carrying substrate layer. In the example of FIG. 7 , thesensor apparatus 700 includes an arrangement of electrodes 716 disposedon a contact surface of a corresponding electrode receiving portion ofthe substrate layer 712. Respective electrodes 716 can operate assensors for measuring electrical activity. Additionally, oralternatively, electrodes 716 can be configured to deliver electricalenergy (e.g., stimulus signals), as described herein. The electrodes 716are coupled to a respective connector 720 through electricallyconductive element (e.g., a trace or wire). The respective connectors720 are adapted to couple to an electrode interface (e.g., interface34), which may be a direct connection or a connection through additionalcabling, to carry signal measurements or provide a stimulus signalsbetween the electrode interface and respective electrodes 716.

By way of further example, FIG. 8 illustrates an image 800 part of apatient's body such as may be acquired by an imaging modality (e.g.,x-ray or fluoroscopy). The image 800 includes an IMD 802 implantedwithin a patient's body. In the example of FIG. 8 , the IMD 802 includesleads 804, 806 and 806 extending from the housing of the IMDelectronics. In the example of FIG. 8 , the IMD 802 includes three leads804, 806 and 806 that are fixed in the patient's body with respect tothe patient's heart. Each of the leads 804, 806 and 806 includes one ormore electrodes for sensing electrical signals and/or deliveringrespective stimulus signals to the heart. The leads 804, 806 and 806 mayinclude respective electrodes in contact with the heart tissue or may beimplemented as non-contact electrodes that deliver stimulus or sensesignals accordingly.

Also shown in FIG. 8 are body surface electrode locations 810distributed across the image 800. The electrode locations 810 may berendered visible in the imaging modality through the use of radio opaquemarkers or otherwise using radio opaque materials to form the bodysurface electrodes.

By way of further example, FIGS. 9 and 10 depict examples of signalvectors 900 and 1000 that may be measured using an IMD (e.g., IMD 12,400, 500, 600, 800) as disclosed herein. In the example of FIG. 10 ,sensing IMD electrodes are located at respective locations 902, 904 and906 to provide a set of vectors, each having a magnitude and direction.For example, the signal vectors may be considered having directionalcomponents in relation to the right arm (RA), left arm (LA) and leftfoot (LF), respectively. The measured signal vectors in FIG. 9 thusrepresent distal-coil measured signal vectors for the electrodelocations. In the example of FIG. 10 , the signal vector also sensingIMD electrodes for electrode locations 1002, 1004 and 1006 in relationto RA, LA, and LF directions, respectively. The signal vectors shown inFIG. 10 thus represents proximal-coil measured signal vectors for theelectrode locations 1002, 1004 and 1006.

FIG. 11 illustrates examples of measured signals 1102 and 1104 for therespective signal vectors shown in FIGS. 9 and 10 . As described herein,the measured signals 1102 and 1104 may be combined with body surfacesignal measurements to augment electrogram reconstructionelectrocardiographic mapping onto one or more surface of interest.

In view of the foregoing structural and functional features describedabove, example methods that can be implemented will be betterappreciated with reference to flow diagram of FIG. 12 . While, forpurposes of simplicity of explanation, the method of FIG. 12 is shownand described as executing serially, it is to be understood andappreciated that such methods are not limited by the illustrated order,as some aspects could, in other examples, occur in different ordersand/or concurrently with other aspects from that disclosed herein.Moreover, not all illustrated features may be required to implement amethod. The methods or portions thereof can be implemented asinstructions stored in one or more non-transitory machine readable mediaas well as be executed by a processor of one or more computer devices,for example.

FIG. 12 depicts an example of a method 1200 to reconstruct electricalactivity on surface of interest using information from an IMD. At 1202,a communications link between a noninvasive cardiac monitoring system(e.g., system 14) and an IMD (e.g., IMD 12). Useful examples of the IMDinclude an implantable cardioverter-defibrillator, a pacemaker or aventricular assist device. These and similar types of devices arecommercially available from Medtronic Corp and other companies. Asdescribed herein, the link may be a direct wireless connection (e.g.,WiFi, Bluetooth, NFC) between the monitoring system and the IMD. Inother examples, the link may be an indirect connection such as through aprogrammer or other device (e.g., network router or an interfacedevice).

At 1204, the method includes receiving IMD data at the monitoring systemvia the communications link. For example, a communications module of theIMD encodes and sends the IMD data, which is received (directly orindirectly) by a communications module of the monitoring system. The IMDdata may represent electrical signals measured by the IMD and/or signalsgenerated by the IMD. The IMD data may also include other associateddata (e.g., data identifying each electrode that provides signalmeasurement, timestamps and the like). The received IMD data may bestored in memory of the monitoring system.

At 1206, the IMD electrical data is synchronized with noninvasiveelectrical measurement data to provide synchronized electrical data. Thesynchronization is performed based on timing of a synchronization signalsensed by one or more IMD electrodes and/or one or more electrodes atbody surface locations. For example, the synchronization signal may be asignal pulse provided by an IMD electrode or an EP electrode, and may bea subthreshold pulse (e.g., does not create an action potential withinthe heart) or be a suprathreshold pulse (e.g., that creates an actionpotential within the heart). The noninvasive electrical data may bestored in memory representing signals generated and/or measured by bodysurface electrodes distributed across a surface of a patient's body,such as described herein. In one example, the synchronization at 1206may be performed for a given measurement interval and provide a commontime zero relative to which the IMD electrical data and the body surfaceelectrical data is aligned. The synchronization may be performed once atthe beginning of an analysis episode or be repeated for each subsequentmeasurement interval. In some examples, the synchronization may beperformed periodically to resynchronize the timing and measurements ofthe IMD and the body surface signal measurements.

At 1208, reconstructed electrical signals are computed for locations ona surface of interest within the patient's body based on thesynchronized electrical data and geometry data. The electrical data andgeometry data can be stored in a non-volatile or volatile memorystructure, which may be local memory to the computer executing theinstructions or distributed memory (e.g., in a network or cloud system).As described, the geometry data may represent locations of the bodysurface EP electrodes, the location of invasive EP electrodes, thelocation of the IMD electrode within the patient's body and spatialconfiguration the surface of interest in three-dimensional space. Forexample, the surface of interest may be one or more surface of the heart(e.g., epicardial and/or endocardial surfaces) or any envelope betweenthe heart and the body surface onto which the electrical signals may bereconstructed. While not shown explicitly in FIG. 12 the method 1200 mayinclude one or more other features described herein.

In an example, the IMD includes an electrode interface (e.g., circuitry)that is coupled to one or more IMD electrodes adapted to be positionedat respective invasive locations within the patient's body. Themonitoring system may be programmed to control the IMD through thecommunications link (e.g., directly or indirectly) to generate thesynchronization signal (e.g., a pulse, such as a pacing spike) via atleast one of the IMD electrodes. Electrical activity is measured by theEP electrodes (e.g., electrodes on the patient's body and/or invasiveelectrodes within the patient's body) responsive to the synchronizationsignal. The measured electrical activity is analyzed to identify afeature of the synchronization signal reflected in the measuredelectrical activity, and the identified feature is used to synchronizethe IMD electrical data with the noninvasive electrical measurementdata.

In another example, monitoring system is programmed to generate thesynchronization signal via one or more EP electrodes. Electricalactivity is measured by IMD electrodes within the patient's bodyresponsive to the synchronization signal. The measured electricalactivity is communicated as IMD data to the monitoring system throughthe communication link and analyzed to identify a feature of thesynchronization signal reflected in the measured electrical activity.The identified feature is used to synchronize the IMD electrical datawith the noninvasive electrical measurement data.

As yet another example, the method 1200 further includes the monitoringsystem controlling the IMD through the communications link to generate acalibration signal by one or more of the IMD electrodes. For example,the monitoring system generates instructions that define parameters fora calibration signal (e.g., pulse width and amplitude), and the IMD(e.g., processor) controls its signal generator to generate acalibration signal responsive to the executing the instructions from themonitoring system. The calibration signal may include one or moresignals generated by one or more IMD electrodes. The electrical activityis measured by the EP electrodes (e.g., electrodes on the patient's bodyand/or invasive electrodes within the patient's body) responsive to thecalibration signal(s). An impedance of the patient's body is determinedbetween the IMD electrode and the electrode surface locations of thepatient's body based on the measured electrical activity and thecalibration signal. Model data is calibrated to characterizeinhomogeneities of the patient's body between the heart and theelectrode locations on the body surface based on the impedance. In someexamples, a user can select a set of which inhomogeneities to include inthe calibrated model data in response to a user input, which can rangefrom using no inhomogeneities (e.g., a homogeneous model) to the mostgranular set of inhomogeneities. The reconstructed electrical signalsmay be computed at 1208 for locations on the surface of interestcomputed based on the calibrated model data as well as electricalmeasurement data (e.g., synchronized IMD data and EP data). For example,the reconstructed electrical signals may be computed by calculating atransfer matrix based on the geometry data and the calibrated modeldata. Regularization further may be used to compute the reconstructedelectrical signals on the surface of interest based on the transfermatrix and the synchronized electrical data.

As an additional or an alternative example, the method 1200 includesdetermining one or more boundary conditions based on geometry datarepresenting a location of one or more IMD electrodes together with theIMD electrical data measured by one or more respective IMD electrodesand/or IMD signals (e.g., having known signal parameters) generated byone or more respective IMD electrodes. The reconstructed electricalsignals are computed on the surface of interest based on thesynchronized electrical data, including electrical signals measured bythe IMD electrodes and the EP electrodes, the geometry data, the atleast one boundary condition being imposed to constrain computationsimplemented to determine the reconstructed electrical signals.

As a further additional or an alternative example, the method 1200employs the monitoring system to control the IMD, via the communicationslink, to generate a stimulus signal via one or more of the IMDelectrodes. For example, the stimulus signal may be delivered by asingle IMD electrode or it may be delivered between one or more pairs ofIMD electrodes as vector signal. In an example, a vector signal may beprovided between IMD electrodes located in the same heart chamber or, inanother example, in different heart chambers. The method thus mayinclude measuring electrical activity at the surface measurementlocations on the patient's body responsive to the stimulus signal, andreconstructed electrical signals are computed on the surface of interestbased on the measured (synchronized) electrical activity and thegeometry data.

In view of the foregoing structural and functional description, thoseskilled in the art will appreciate that portions of the invention may beembodied as a method, data processing system, or computer programproduct. Accordingly, these portions of the present invention may takethe form of an entirely hardware embodiment, an entirely softwareembodiment, or an embodiment combining software and hardware.Furthermore, portions of the invention may be a computer program producton a computer-usable storage medium having computer readable programcode on the medium. Any suitable computer-readable medium may beutilized including, but not limited to, static and dynamic storagedevices, hard disks, optical storage devices, and magnetic storagedevices.

Certain embodiments of the invention have also been described hereinwith reference to block illustrations of methods, systems, and computerprogram products. It will be understood that blocks of theillustrations, and combinations of blocks in the illustrations, can beimplemented by computer-executable instructions. Thesecomputer-executable instructions may be provided to one or moreprocessor of a general purpose computer, special purpose computer, orother programmable data processing apparatus (or a combination ofdevices and circuits) to produce a machine, such that the instructions,which execute via the processor, implement the functions specified inthe block or blocks.

These computer-executable instructions may also be stored incomputer-readable memory that can direct a computer or otherprogrammable data processing apparatus to function in a particularmanner, such that the instructions stored in the computer-readablememory result in an article of manufacture including instructions whichimplement the function specified in the flowchart block or blocks. Thecomputer program instructions may also be loaded onto a computer orother programmable data processing apparatus to cause a series ofoperational steps to be performed on the computer or other programmableapparatus to produce a computer implemented process such that theinstructions which execute on the computer or other programmableapparatus provide steps for implementing the functions specified in theflowchart block or blocks.

What have been described above are examples. It is, of course, notpossible to describe every conceivable combination of components ormethods, but one of ordinary skill in the art will recognize that manyfurther combinations and permutations are possible. Accordingly, theinvention is intended to embrace all such alterations, modifications,and variations that fall within the scope of this application, includingthe appended claims. Where the disclosure or claims recite “a,” “an,” “afirst,” or “another” element, or the equivalent thereof, it should beinterpreted to include one or more than one such element, neitherrequiring nor excluding two or more such elements. As used herein, theterm “includes” means includes but not limited to, the term “including”means including but not limited to. The term “based on” means based atleast in part on.

What is claimed is:
 1. A system comprising: an implantable medicaldevice (IMD) comprising an IMD electrode and IMD circuitry, wherein theIMD electrode is adapted to be positioned within a patient's body, andthe IMD circuitry is coupled to the IMD electrode and adapted to provideIMD electrical data based on an electrical signal sensed by the IMDelectrode and to deliver an electrical signal through the IMD electrode;and an electrophysiology (EP) monitoring system comprising:non-transitory memory to store the IMD electrical data, EP electricaldata, and geometry data, the EP electrical data representing signalsmeasured by EP electrodes; and a processor coupled to the memory toaccess data and instructions stored in the memory, the instructionsprogrammed to at least: establish a communications link between the EPmonitoring system and the IMD; receive the IMD electrical data at the EPmonitoring system through the communications link; analyze the IMDelectrical data and the EP electrical data to identify a feature of atleast one signal represented by the IMD electrical data and the EPelectrical data; synchronize the IMD electrical data and the EPelectrical data based on the identified feature and provide synchronizedelectrical data representative of time-synchronized electrical signalssensed by the IMD electrode and the EP electrodes; and compute a map ofelectrical signals for locations on a surface of interest within thepatient's body based on the synchronized electrical data and thegeometry data, the geometry data representing locations of the EPelectrodes, a location of the IMD electrode, and geometry of the surfaceof interest.
 2. The system of claim 1, wherein the identified feature ofthe EP signal includes a morphology and/or timing of the at least onesignal.
 3. The system of claim 1, wherein the IMD includes a pluralityof IMD electrodes adapted to be positioned at respective locationswithin the patient's body, and the instructions are further programmedto: control the IMD through the communications link to providerespective signals from different ones of the IMD electrodes; storeelectrical signal data measured by the EP electrodes responsive to therespective signals; and reconstruct EP signals across the surface ofinterest based on the stored electrical signal data measured by the EPelectrodes, responsive to the respective signals and the geometry data,in which the reconstructed EP signals are representative of effects ofeach of the respective signals on cardiac tissue.
 4. The system of claim3, wherein: the respective signals are provided by the IMD with varyingsignal parameters, and the reconstructed EP signals at one or moreregions that are representative of the effects of each of the respectivesignals at locations different from where the respective signals areapplied and/or across an entire surface of the patient's heart.
 5. Thesystem of claim 3, wherein the respective signals are respective pacingsignals applied at the different locations corresponding to thelocations of the electrodes, and the instructions are further programmedto: compute an impedance correction matrix based on EP electrical datameasured responsive to the pacing signals applied at each of thedifferent locations; and correct regions across the surface of interest,which were not paced, based on the impedance correction matrix.
 6. Thesystem of claim 5, wherein the instructions are further programmed to:calibrate model data to characterize inhomogeneities of the patient'sbody between the surface of interest and an outer surface of thepatient's body based on the impedance correction matrix, and compute themap of electrical signals for locations residing on the surface ofinterest based on the calibrated model data.
 7. The system of claim 6,wherein the instructions are further programmed to: calculate a transfermatrix based on the geometry data and the calibrated model data, whereinthe map of electrical signals comprises a map reconstructed electricalsignals on the surface of interest computed based on the transfer matrixand the synchronized electrical data.
 8. The system of claim 1, whereinthe instructions are further programmed to: send program instructions tothe IMD over the communications link to control the IMD to provide astimulus signal from the IMD electrode to implement a cardiac therapybased on control parameters included in the program instructions;generate the map of electrical signals representative of cardiacelectrical activity responsive to the control parameters; repeat thesending of program instructions and generating the map to providerespective maps of electrical signals across for different controlparameters; and determine a set of the control parameters to configurethe IMD to implement the cardiac therapy based on an evaluation of therespective maps.
 9. The system of claim 1, wherein the instructions tocompute the map of electrical signals for locations residing on thesurface of interest include instructions to reconstruct the electricalsignals on the surface of interest by solving an inverse problem basedon the geometry data and the synchronized electrical data, theinstructions are further programmed to: spatially align a region orpoints in the reconstructed electrical signals corresponding to one ormore cardiac locations where an instance of a cardia event recorded bythe IMD electrode was represented in the IMD electrical data; andcompare the reconstructed electrical signals for an other detectedinstance of the cardiac event with a prior instance of the cardiac eventto determine an accuracy of the reconstructed electrical signals. 10.The system of claim 9, wherein the instructions are further programmedto adjust the instructions to reconstruct the electrical signals basedon the comparison so that the reconstructed electrical signals bettermatch signals recorded by the IMD for the event.
 11. The system of claim10, wherein the instructions to adjust the instructions are furtherprogrammed to adjust the reconstructed electrical signals spatially tominimize a difference between the reconstructed electrical signals andthe signals recorded by the IMD for the other detected instance of thecardiac event.
 12. The system of claim 10, wherein the instructions toadjust are further programmed to weight respective locations in atransfer function used to solve the inverse problem based on acorrelation between locations of reconstructed signals and the signalsrecorded by the IMD, and using the adjusted weights in the transferfunction to reconstruct the electrical signals on the surface ofinterest.
 13. The system of claim 1, wherein the IMD comprises aleadless IMD.
 14. The system of claim 1, further comprising: anon-invasive sensor apparatus including respective EP electrodes, thesensor apparatus configured to position the respective electrodes on thesurface of the patient's body; and a communications module configured tocommunicate with the IMD over the communications link.
 15. One or morenon-transitory computer-readable media having instructions, which whenexecuted by a processor, cause the processor to at least: establish acommunications link between an electrophysiological (EP) monitoringsystem and an implantable medical device (IMD) including an IMDelectrode; receive IMD electrical data at the EP monitoring systemthrough the communications link; analyze the IMD electrical data and theEP electrical data to identify a feature of at least one signalrepresented by the IMD electrical data and the EP electrical data;synchronize the IMD electrical data and the EP electrical data based onthe identified feature and provide synchronized electrical datarepresentative of time-synchronized electrical signals sensed by the IMDelectrode and the EP electrodes; and compute a map of electrical signalsfor locations residing on a surface of interest within a patient's bodybased on the synchronized electrical data and geometry data, thegeometry data representing locations of the EP electrodes, a location ofthe IMD electrode, and geometry of the surface of interest.
 16. Themedia of claim 15, wherein the IMD includes a plurality of IMDelectrodes, and the instructions are further programmed to: control theIMD through the communications link to provide respective signals fromdifferent ones of the IMD electrodes; store electrical signal datameasured by the EP electrodes responsive to the respective signals; andreconstruct EP signals across the surface of interest based on thestored electrical signal data measured by the EP electrodes, responsiveto the respective signals and the geometry data, in which thereconstructed EP signals are representative of effects of each of therespective signals on cardiac tissue.
 17. The media of claim 16, whereinthe respective signals are applied at different locations correspondingto locations of the electrodes, and the instructions are furtherprogrammed to: compute an impedance correction matrix based on EPelectrical data measured responsive to the respective signals applied ateach of the different locations; correct regions across the surface ofinterest, which were not paced, based on the impedance correctionmatrix; calibrate model data to characterize inhomogeneities of thepatient's body between the surface of interest and the surface of thepatient's body based on the impedance correction matrix, and compute themap of electrical signals for locations residing on the surface ofinterest based on the calibrated model data.
 18. The media of claim 15,wherein the instructions are further programmed to: send programinstructions to the IMD over the communications link to control the IMDto provide a stimulus signal from the IMD electrode to implement acardiac therapy based on control parameters included in the programinstructions; generate the map of electrical signals representative ofcardiac electrical activity responsive to the control parameters; repeatthe sending of program instructions and generating the map to providerespective maps of electrical signals across for different controlparameters; and determine a set of the control parameters to configurethe IMD to implement the cardiac therapy based on an evaluation of therespective maps.
 19. The media of claim 15, wherein the instructions tocompute the map of electrical signals for locations residing on thesurface of interest include instructions to reconstruct the electricalsignals on the surface of interest by solving an inverse problem basedon the geometry data and the synchronized electrical data, theinstructions are further programmed to: spatially align a region orpoints in the reconstructed electrical signals corresponding to one ormore cardiac locations where an instance of a cardiac event recorded bythe IMD electrode was represented in the IMD electrical data; comparethe reconstructed electrical signals for an other detected instance ofthe cardiac event with a prior instance of the cardiac event todetermine an accuracy of the reconstructed electrical signals; andadjust the instructions to reconstruct the electrical signals based onthe comparison so that the reconstructed electrical signals better matchthe signals recorded by the IMD for the event.
 20. The media of claim19, wherein the instructions to adjust are further programmed to weightrespective locations in a transfer function used to solve the inverseproblem based on a correlation between locations of the reconstructedelectrical signals and the signals recorded by the IMD, and using theadjusted weights in the transfer function to reconstruct the electricalsignals on the surface of interest.